Cystic fibrosis (CF) is the most common lethal genetic disorder in Caucasians. Although individuals with CF are living longer, with median survival now exceeding 38 years, the most common cause of death remains respiratory failure due to lung infection. Methicillin-resistant Staphylococcus aureus (MRSA) is emerging in CF as an especially important infectious bacteria. The prevalence of MRSA pulmonary infection in the CF population has dramatically increased over the last twenty years, from less than 5% to now 25.7% of patients. Moreover, MRSA infection has clinically significant effects on outcomes in CF, resulting both in a more rapid decline in lung function and decreased survival among patients with persistently positive MRSA respiratory cultures. Studies have demonstrated that approximately one-third of the CF patients who acquire MRSA are only transiently infected and do not have significant clinical effect, whereas two-thirds of patients remain persistently infecte and have associated poor outcomes. The purpose of this project is to identify specific patient and bacterial characteristics that contribute to and predict the likelihood of persistent MRSA infection in individuals with cystic fibrosis. To do so, this project will use the National Cystic Fibrosis Patient Registry-a large database that collects information on over 80% of the CF patients in the United States. This database will be examined in order to identify certain patient characteristics that are associated with persistent MRSA infection. Additionally, MRSA from CF patients with known persistent infections will be compared to MRSA from CF patients with transient infections. By comparing the molecular properties of these two groups of MRSA bacteria, this project aims to identify those characteristics that are associated with persistent infection. With the recent recognition of the significance of MRSA infection in cystic fibrosis, there is acknowledgement amongst the CF care/research community that ongoing research is needed in order to determine how best to manage this clinically important issue in CF treatment. This study aims to characterize both patient and pathogen characteristics that are associated with persistent MRSA infection and the related worse clinical outcomes. Ultimately, the intent is that this research project can provide the foundation for further work that will continue to work toward deciphering which individuals with CF will need aggressive treatment of MRSA infection, with the goal of preventing the more rapid loss of lung function and the increased risk of death that are associated with this serious and increasingly prevalent infection.